Sample Required?

Test Preparation Needed?

None

The Test Sample

What is being tested?

This test detects characteristic changes (rearrangements) in specific genes in B-cells. This information can be helpful in diagnosing a B-cell lymphoma.

B-cells are a type of lymphocyte (a kind of white blood cell, WBC) that produces antibodies in response to infections or other "foreign invaders." Rearrangements in certain parts of their DNA called immunoglobulin genes are a normal part of their development. These rearrangements are associated with the development of a large repertoire of diverse B-cells, allowing them to protect against many different kinds of infections. The final order in which the genes are rearranged is called a gene rearrangement profile. Within any normal population (sample) of B-cells, the cells and their gene rearrangement profiles are very diverse.

In a lymphoma, the B-cells in affected tissue (such as blood, bone marrow or lymph node) are identical and their gene rearrangement profiles are likewise identical. Lymphomas arise when an abnormal B-cell begins to produce numerous identical copies of itself (clones). The cloned cells grow and divide uncontrollably, crowding out normal cells.

A B-cell immunoglobulin gene rearrangement test evaluates the B-cells in a person's sample to determine whether the majority of B-cell rearrangement profiles are diverse or identical. This information, along with clinical signs and symptoms and results of other laboratory tests, can help clarify a person's diagnosis, or evaluate the persistence or recurrence of lymphoma.

About 85% of non-Hodgkin lymphomas in the U.S. are B-cell lymphomas, according to the American Cancer Society (ACS).

How is the sample collected for testing?

A bone marrow or other tissue biopsy procedure is performed by a doctor or other trained specialist. Body fluid samples are obtained by inserting a needle into the body cavity and withdrawing a portion of the fluid with a syringe. Sometimes, a blood sample is obtained by inserting a needle into a vein in the arm.

Is any test preparation needed to ensure the quality of the sample?

The Test

How is it used?

B-cell immunoglobulin gene rearrangement tests are used to help diagnose non-Hodgkin B-cell lymphomas and evaluate for residual or recurrent disease after treatment.

Lymphomas arise when an abnormal B-cell begins to produce numerous identical copies of itself (clones). The cloned cells grow and divide uncontrollably, crowding out normal cells. There are many different types of B-cell lymphoma and each has different characteristics, prognoses, and a likely response to therapy. Several classification systems have been used to describe them. The most recent is the World Health Organization's (for more on this, see the Lymphoma article).

If indicated, immunophenotyping is performed on blood, bone marrow, or other tissue (e.g., enlarged lymph node, tumor) using a method such as flow cytometry or immunohistochemistry. This test detects the presence or absence of certain markers on the membrane of the cells or inside the cells. These commonly used markers are called clusters of differentiation (CD) and are listed numerically. Patterns of antigens (presence or absence) can provide information as to whether the B-cells are clones (monoclonal) and can further help classify a B-cell lymphoma.

A proliferation of B-cells can be benign or malignant. If, at this point, there is still no conclusion whether a person has a benign or malignant lymphocyte population, B-cell immunoglobulin gene rearrangement testing can be performed.

Testing may sometimes be performed to evaluate the effectiveness of lymphoma treatment, that is, to detect residual or recurrent disease, the continued presence of abnormal monoclonal B-cells.

With immunophenotyping (e.g., flow cytometry, immunohistochemistry), antigen groupings that are inconclusive for a B-cell lymphoma, or when the doctor wants to confirm a diagnosis of lymphoma based on histopathology and immunophenotyping

Testing may also be ordered when a person has been treated for a lymphoma to evaluate the effectiveness of treatment, that is, to detect residual or recurrent disease.

What does the test result mean?

Results of testing are typically interpreted by a doctor who specializes in pathology, in particular, pathology dealing with blood, blood cells, and bone marrow cells (hematopathology). Results must be interpreted in conjunction with clinical findings, other test results including pathology immunophenotyping information, an understanding of the strengths and limitations of different testing methods, and with an understanding of the range of findings in a "normal" lymphocyte cell population.

In general, if a significant clonal B-cell population is detected and other associated tests are in agreement, then it is likely that the individual tested has a B-cell lymphoma.

Examples of lymphomas that may be detected by gene rearrangement testing include:

Is there anything else I should know?

According to the American Cancer Society (ACS), non-Hodgkin lymphoma (NHL) is one of the most common cancers in the United States. ACS estimates that about 70,130 people will be diagnosed with NHL in 2012 and as many as 18,940 will die of it.

Sample collection and testing may need to be repeated when the initial sample does not contain enough DNA to test.

The detection of a clonal immunoglobulin gene rearrangement is not synonymous with the presence of B-cell lymphoma. An individual may have a clonal B-cell population and not have cancer. Conditions such as autoimmune disorders, immune suppression, and immune deficiencies are sometimes associated with small clonal B-cell populations. This means that one or more groups of cloned B-cells may be present in a person's lymphocyte population without it being considered a lymphoma.

If a person is negative for a clonal B-cell immunoglobulin gene rearrangement, the person may still have lymphoma. A test may also be negative if the test method is not sensitive enough to detect the rearrangement, or if the clonal lymphocytes from the person tested have mutations that are not detected by the test.

Since false positive and false negative results can be associated with this testing, the results must be interpreted in the context of other clinical and pathologic findings.

Since plasma cells are terminally differentiated B-cells, immunoglobulin gene rearrangement testing can also be seen in plasma cell neoplasms, such as multiple myeloma and plasmacytoma.

1. Should everyone with a B-cell lymphoma have B-cell gene rearrangement testing?

2. Can results of testing be used to determine the course of my cancer?

No. A positive testing result only helps to confirm a diagnosis of B-cell lymphoma and does not point to a specific subtype of B-cell lymphoma. The clinical course and response to treatment are generally determined by the subtype of a person's lymphoma, along with certain genetic abnormalities.

3. How common are B-cell gene rearrangements?

B-cell immunoglobulin genes are constantly rearranging themselves to produce unique immunoglobulins. These rearrangements are normal. The immunoglobulin genes consist of numerous, discontinuous coding segments. As B-cells develop and mature, a portion of DNA that contains one full DNA sequence of one of the genes breaks into pieces. After rearrangement, only some of the pieces are kept, which are joined back together in a specific set of steps. To visualize this, imagine that you have a piece of paper with a set of instructions on it, several paragraphs long and containing hundreds of words. Now imagine that you pick and choose words from multiple locations on the page – a sufficient number to form a sentence. Then you get rid of the rest of the words and put together your sentence. You started with a page and ended up with a sentence, but both make sense as you read them and, in this case, both represent "functional genes." It is not hard to see that many different sentences could have been constructed from the same set of instructions. In a similar fashion, the B-cell customization process can be used to produce a large number of unique B-cell gene arrangements.

Ask a Laboratory Scientist

Form temporarily unavailable

Due to a dramatic increase in the number of questions submitted to the volunteer laboratory scientists who respond to our users, we have had to limit the number of questions that can be submitted each day. Unfortunately, we have reached that limit today and are unable to accept your inquiry now. We understand that your questions are vital to your health and peace of mind, and recommend instead that you speak with your doctor or another healthcare professional. We apologize for this inconvenience.

This was not an easy step for us to take, as the volunteers on the response team are dedicated to the work they do and are often inspired by the help they can provide. We are actively seeking to expand our capability so that we can again accept and answer all user questions. We will accept and respond to the same limited number of questions tomorrow, but expect to resume the service, 24/7, as soon as possible.

Article Sources

NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Proudly sponsored by ...

Learn more about ...

Get the Mobile App

Follow Us

This article was last reviewed on August 7, 2012. | This article was last modified on May 13, 2014.

The review date indicates when the article was last reviewed from beginning to end to ensure that it reflects the most current science. A review may not require any modifications to the article, so the two dates may not always agree.

The modified date indicates that one or more changes were made to the article. Such changes may or may not result from a full review of the article, so the two dates may not always agree.